The present invention relates to benzhydrol-pyrazole derivatives and related compounds having kinase inhibitory activity, as well as their therapeutic, diagnostic, and medical uses.
Bruton agammaglobulinemia tyrosine kinase (Btk or BTK) is a cytoplasmic kinase in the Tec family. Btk plays an important role in the development and regulation of lymphoid, myeloid, and mast cell lineages, such as by activating the B-cell receptor (BCR) signaling pathway, mediating cytokine receptor signaling, and participating in mast cell activation. However, activation or overactivation of Btk can contribute to or promote numerous diseases, including B-cell malignancies (e.g., Hodgkin's lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukemia), inflammatory or autoimmune disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, or multiple sclerosis), and mast cell malignancies (e.g., pancreatic insulinoma). Thus, there is a need for new compounds that inhibit Btk and treatment methods using such compounds.